Stop the machine takes Gene Transcription, to cross the occurrence of DNA
Hodges is in the group of Biophysics graduate and Bintu is a graduate student in physics. Both are part of the Laboratory of Jason L. Bustamante choy single molecule biophysics, named for a graduate student in chemistry who died in a car accident in 2005. Bustamante is a professor of physics, chemistry and Molecular and Cellular Biology, Howard Hughes Medical Institute and an affiliate of the California Institute for Quantitative Biosciences (QB3).The researchers also drew on both ends of a DNA molecule after transcription to see what had happened to the nucleosome. They found that the nucleosome was often expelled from the DNA because the tension prevented the DNA to form loops that would have allowed the nucleosome to skip Pol II.
The main obstacle to the success of Pol II is the nucleosome, a bundle of eight histones around which DNA wraps tightly. Tens of thousands of nucleosomes are clustered on a chromosome, efficiently packaging six feet of DNA in a nucleus of one million times smaller. The researchers were able to place a single nucleosome in front of the polymerase and then use optical tweezers to observe what happens when the polymerase encounters the obstacle.
‘These experiments give a much more dynamic of the nucleosome, showing that this is not a static beads on a string, but an active structure that can adjust when and how our genetic information is read,’ said Bintu. ‘C is only a single nucleosome, but the first step in understanding epigenetic effects that make a cell behave differently from another.’
The body of nanomachines that read our genes do not work and as previously thought, according to a new study by University of California, Berkeley, scientists.
Bintu noted that this movement to stop 20-50 steps forward, then a couple of steps back could be a key element of how gene expression is regulated. Nucleosomes are highly regulated by other proteins and may provide signals that control Pol II, just like a traffic light controls the traffic, he said. Regulatory proteins can bind to DNA in the nucleosome and relax more easily, or it could cling to the Pol II and prevent the decline. In both cases it would have accelerated the transcription, while regulatory proteins that compact DNA and nucleosomes further slow or even stop transcription.
Scientists have thought for years that nucleosomes must be ‘relaxed’ to allow gene expression, and the authors note that their results provide a more detailed mechanistic view in this process.
On the other hand, disturbances in nucleosome regulation could lead to disease.
Hodges and Bintu compare the DNA of the nucleosome to a band of adhesive Velcro loop a couple of times around the histones. DNA is constantly pushed, though, and tends to break away and then choose the histones. When the DNA is bound to histones, Pol II can not read the transcript, and breaks. At some point, the nucleosome more than Pol II and nanomachines lanterns along smoothly.
‘We found that even a small amount of tension in the DNA from March to May during transcription results in Pol II piconewtons removing the nucleosome from DNA like a pair of wire strippers,’ said Hodges. ‘It ‘very likely that the DNA of our body is very tense in some places and loose in others, so we believe that it is possible that the cell uses tension in the genome to alter the dynamics of nucleosomes in certain genes.’
When these nanoscale protein machines encounter obstacles that move along the DNA, they stall, often for long minutes, and even go back because transcribing DNA is tightly coiled to fit in the cell nucleus.
The measures, which employed optical tweezers to grab both the polymerase and the end of a single DNA molecule, are reported in the July 31 issue of Science magazine.
‘Transcription is a central point of control for gene expression, since everything from coordinating the development of the prevention of uncontrolled cell growth is cancer, has a highly regulated program of transcription by Pol II,’ said Bintu .
‘When transcription goes haywire, pathologies such as cancer and developmental abnormalities usually follow.’